Electrical stimulation for preservation and restoration of diaphragm function

ABSTRACT

A system and method are presented that electrically stimulates the phrenic nerve whereby said stimulation results in muscle activation of the diaphragm as observed by a measurement of work or power of breathing associated with the inspiratory portion of a stimulated breath.

CROSS REFERENCE TO RELATED CASES

The present application claims priority to the following provisionalapplications: U.S. 62/267,095, entitled: Magnetic Stimulation forControl of the Lung Diaphragm, filed on Dec. 14, 2015; U.S. 62/362,250,entitled: Multiple Electrode Lead System, filed on Jul. 14, 2016; U.S.62/359,972, entitled: Device and Method for Treatment of VentilatorInduced Diaphragm Atrophy, filed on Jul. 8, 2016; U.S. 62/342,345,entitled: Phrenic Nerve Stimulation and Diaphragmatic Pacing System andMethod, filed on May 27, 2016; U.S. 62/316,879, entitled: PeripheralNerve Stimulator and Method, filed Apr. 1, 2016; U.S. 62/304,509,entitled: Method and Apparatus for Stimulating Peripheral Nerves, filedon Mar. 7, 2016; U.S. 62/276,387, entitled: Subcutaneous ElectricalStimulation for Control of the Lung Diaphragm, filed on Jan. 8, 2016;and U.S. 62/387,262, entitled: Temporary Electrical Stimulation forControl of the Lung Diaphragm, filed on Dec. 23, 2015. The entirecontents of each of the above referenced provisional applications beingincorporated herein by reference.

FIELD OF THE INVENTION

Embodiments of the present disclosure are directed to medical devices,systems and their methods of use for providing noninvasive percutaneousand subcutaneous electrical stimulation to a patient subjected tomechanical ventilation, in order to mitigate the effects ofventilator-induced diaphragmatic dysfunction. Embodiments includedevices for controlling, activating, and otherwise interacting with thephrenic nerve, and thereby the diaphragm, of a patient while the patientis undergoing mechanical ventilation.

BACKGROUND

Mechanical ventilation (MV) is used clinically to maintain gas exchangein patients that require assistance in maintaining adequate alveolarventilation. Common indications for MV include respiratory failure,heart failure, surgery, etc. Although MV can be a life-savingintervention for patients suffering from respiratory failure, prolongedMV can promote diaphragmatic atrophy and contractile dysfunction, whichis referred to as ventilator-induced diaphragm dysfunction (VIDD).Extended time on the ventilator may result in VIDD and thereby increasehealth care costs and greatly increase patient morbidity and mortality.Research reveals that 18-24 h on MV is sufficient to develop VIDD inboth laboratory animals and humans.

2.1 million patients are ventilated in United States each yearrepresenting 36% of the ICU population. The estimated annual cost tomanage ventilated patients in the US each year is 27 billionrepresenting 12% of all hospital costs. It has been found thatapproximately 60% of the ICU patient population intubated are scheduledfor extubation and weaning. Unfortunately, nearly 45% of patientsreceiving invasive ventilation therapy in the ICU have difficultyweaning and develop some form of dependency on the ventilator. Thisoften leads to the need to extend the patients ICU/CCU stay beyond whatis typically required for the original medical condition since manyencounter prolonged weaning periods. The projected number of patientsrequiring prolonged acute mechanical ventilation on an annual basis inthe US is expected to grow to be greater than 600,000 patients by theyear 2020 with the overall cost of managing these patients exceeding $64billion.

Animal models have shown that maintaining some level of stimulation tokeep the diaphragm working when on a ventilator is enough to prevent orreduce atrophy. Unfortunately having a patient breath spontaneously orin assist mode from the initiation of ventilation is not always possibledue to the level of sedation and/or disease state.

In these cases, phrenic nerve pacing is a viable alternative to controlthe level of effort exerted by the patient and also in cases where thepatient has become ventilator dependent and requires a training regimeof pacing to strengthen their muscles. Phrenic nerve pacing in animalshas also been shown to prevent diaphragm atrophy. Pacing the phrenicnerve in patients who suffer from spine injury who have lost the abilityto breath, has be shown to reverse the effect of atrophy over a 6 monthstraining period where the diaphragm has not been used in years. It isgenerally better to prevent a disease condition rather than remediateit. Initiating stimulation early in the regime of ventilation will mostlikely have the most profound effect on reducing time to extubation.

Methods currently exist to electrically stimulate the phrenic nerve inchronically ventilated patients as an alternative to mechanical positivepressure ventilation, to avoid some of the potential side effects oflong term ventilation already mentioned. More recently central sleepapnea events have been reduced with the use of implanted phrenic nervepacing at the onset of apnea. Phrenic nerve pacing has also beenachieved with the use of trans venous electrical stimulation. Patientswho have permanent respiratory insufficiency due to absence or reductionin a central respiratory drive descending from the brain stem (C3, C4and C5) are now using commercially available pacing products to pace thediaphragm muscle by electrically stimulating the phrenic nerves usingimplanted electrodes. These implanted stimulation devices use some formof phrenic nerve cuffs, or diaphragm electrodes all of which requireinvasive surgeries. The feasibility of such techniques to preventdiaphragm atrophy or wean patients from a ventilator are limited by thecost and risks associated with permanently implanted phrenic nervepacing electrodes and are not a viable alternative for VIDD patients.

Diaphragm muscle pacing, phrenic nerve pacing, and combined intercostaland unilateral diaphragm pacing techniques are currently being used towean patients without respiratory drive from ventilators in the chronicsetting of ventilation and reduce the incidence of infection,atelectasis, and respiratory failure. There exists the need for a shortterm pacing alternative which can be easily connected to a patient inthe ICU or post-surgery or similar setting to wean or prevent VIDD fromoccurring.

Embodiments described herein seek to meet this need by providing adiaphragmatic stimulation system which includes an electrical lead(s)component that is readily employed without the need of a permanent orsurgical implantation. The system measures the level of effort in thepatient's breathing. The level of stimulation is titrated with thatlevel of effort measurement. Taken together these embodiments provide aless invasive system that can accommodate modest patient motion andfunction well within the context of a surgical or ICU recovery setting.

Embodiments of the present disclosure provide a system and methods ofits use which when properly utilized, reduce the occurrence of VIDD byproviding stimulation to the diaphragm of a patient undergoing MV andthereby provide improved patient outcomes if/when transitioning from MVand provide reduced healthcare costs.

SUMMARY

Embodiments of the system disclosed herein may be collectively referredto as a Percutaneous Electrical Phrenic Nerve Stimulation (PEPNS)system. Embodiments of the PEPNS system include both medical devices aswell as methods of using those devices to provide stimulation and/orpacing to the diaphragm of a patient via electrical stimulation of thephrenic nerve so as to aid in preventing the occurrence of VIDD and towean a patient from a mechanical ventilator. The PEPNS system includes apulse generator console (or stimulator), called theStimulator/Controller (S/C) throughout the disclosure, lead electrodesconnected to the console for stimulating the phrenic nerve, as a well asa wye flow and pressure sensor that is used for detecting theinspiration and exhalation from the patient and measuring pressure atthe ventilator pneumatic circuit wye.

In use, the wye flow and pressure sensor are supplied and insertedbetween a mechanical ventilator and the patient. The wye provides flowand pressure information to the console. A graphical user interface(GUI) on or adjacent to the console is used to permit physician ortechnician interaction with the stimulator. In general, the physicianwill set electrical pulse parameters and observe measurements on theGUI.

The leads of the system include two sets of multiple stimulationelectrodes connected to the stimulator console by cables. The leads areinserted subcutaneously into the patient's neck and positioned adjacentto the phrenic nerve. The stimulator is then activated by the operatingphysician or technician to provide electrical pulse(s) to the phrenicnerve, and thus stimulate the diaphragm. Electrical pulses are deliveredto the phrenic nerve by those electrodes along the leads that are in anoptimized position adjacent to the nerve.

As the patient is transitioned from a fully ventilator dependent statethe present system will shorten the weaning period and provide patientspecific information to the physician to allow a rapid and accurateassessment of the patient's readiness to come off the mechanicalventilator.

BRIEF DESCRIPTION OF THE DRAWINGS

Throughout the several views of the drawing identified below referencenumerals indicate identical structures.

FIG. 1a is a schematic view of an embodiment of the PEPNS system shownin use with a patient and ventilator.

FIG. 1b is a view of an embodiment of the insertion needle used ininitial phrenic nerve location.

FIG. 2a is a schematic view of one embodiment of the four electrode(pole) lead of the lead system component of the PEPNS system shown inFIG. 1 a.

FIG. 2b is a schematic and block diagram view showing the electricalrelationship between an embodiment of the lead system and the C/S asseen in FIGS. 1a and 2 a.

FIG. 2c is a chart comparing work with applied stimulation.

FIG. 3 is a close up sectional anatomic view of the patient's neck shownin FIG. 1 with additional anatomy dissected to the proper positioning ofa lead relative thereto.

FIG. 4 is a detailed but schematic view of the lead shown in FIG. 3depicting the proximity of individual electrodes to the phrenic nervebody.

FIG. 5 is a detailed view of the image shown in FIGS. 3-4 with morecomplete anatomical detail of the relative position of the first lead tothe phrenic nerve illustrated.

FIG. 6 is the same view of the patient anatomy shown in FIG. 5 but withthe potential for repositioning the lead being depicted.

FIGS. 7-10 depict a method of inserting a lead into the neck of thepatient shown in FIG. 1 a.

FIG. 11 is a sequence of graphical panels depicting waveforms associatedwith a flow control regimen of the mechanical ventilator and the PEPNSsystem shown in FIG. 1 a.

FIG. 12 is a series of graphical panels depicting waveforms associatedwith a pressure control regimen of a mechanical ventilator and the PEPNSsystem shown in FIG. 1 a.

FIG. 13 is a series of graphical panels depicting waveforms associatedwith a Synchronized Intermittent Mandatory Ventilation (SIMV) mode in aflow control regimen with pressure support ventilation in use with thePEPNS system shown in FIG. 1 a.

FIG. 14 is a series of graphical panels depicting waveforms associatedwith a (SIMV) mode in a pressure control regimen with pressure supportventilation as may be used with the PEPNS system shown in FIG. 1 a.

FIG. 15 is a series of graphical panels depicting waveforms associatedwith a bi-level ventilator modality with pressure support ventilation asmay be used with the PEPNS system shown in FIG. 1 a.

FIG. 16 is a series of graphical panels depicting waveforms associatedwith a pressure regulated volume ventilation setting of the mechanicalventilator in use with the PEPNS system shown in FIG. 1 a.

FIG. 17A depicts breathing waveforms and measurements of work using twodifferent techniques.

FIG. 17 B is a table that shows calculated differences between the twodifferent techniques set forth in FIG. 17A.

FIG. 18 is a presentation of animal data in the form of waveformsmeasured during periodic stimulation of a sedated pig.

FIGS. 19A-19C are tables that reflects the input parameters to thegraphic user interface of the stimulator/controller.

FIG. 20A, FIG. 20A-1, and FIG. 20A-2 is a table of alarm conditions.

FIG. 20B is a table of alarm conditions.

DETAILED DESCRIPTION OF THE DRAWINGS

In FIG. 1a an embodiment of the PEPNS system 10 is shown in a typicalenvironment of use. As is shown the PEPNS system 10 includes anoperating console or stimulator/controller 12 which is in communicationwith an instrumented wye sensor 14 and an electrical stimulation leadassembly 16.

In order to stimulate the diaphragm 20 of a patient 22 the lead system16 must be properly positioned percutaneously in the neck 18 of apatient 22. Current from the lead system electrically stimulates thephrenic nerve. To monitor the patient and determine that the level ofstimulation is in fact sufficient to move the patients diaphragm 20 inthe manner desired, the instrumented wye sensor 14 is placed in thebreathing circuit tubing 26 of the mechanical ventilator 30 (MV) andmeasurements carried out by the S/C 12.

The instrumented wye sensor is pneumatically connected to the MV tubecircuit 26 to measure both flow and pressure in the wye 24. There are anumber of alternative methods for positioning sensors for measuring wyeflow and pressure. The wye sensor 14 is electrically coupled to thestimulator/controller 12. The stimulator/controller 12 has processor orCPU 31 and an integrated pulse generator 32 to supply an electricaloutput delivered to the lead system 16 via a lead cable 34.

Data received from the wye sensor 14 and lead system 16, as well as theoutput parameters of the pulse generator 32 are displayed on a displayor graphical user interface (GUI) 33 of the stimulator/controller 12.The GUI 33 may be a separate unit or device, such as a monitor, or maybea dedicated component of the stimulator/controller 12. It will likelyhave both a touch screen for entering information and a high resolutiondisplay for displaying various information to the user.

Turning now to the lead system 16, as mentioned above the lead system 16comprises a unitary lead body having a distal end with at least fourelectrodes and a proximal end having a set of terminals for connectionto the S/C. In the embodiment shown in FIG. 2a , the lead 36 is amultipolar lead having at least four electrodes 38 (a-d) containedwithin a lead body 35. Each electrode is in communication with thestimulator/controller 12 (see FIG. 1a ) via lead cable 34 (see FIG. 1a). By providing each lead 36(a-b) with multiple electrodes (or poles) 38ensures that at least one pair of electrodes will lie close to and crossthe phrenic nerve 42 which from here on will be referred to as traverseto the nerve in the manner shown in FIGS. 3-6 at all times after thelead is inserted or subsequently repositioned due to neck motion orrepositioning of the patient (patients are routinely repositioning inthe ICU to prevent bedsores). By placing the leads 36 transverse to thenerve 42 a pair of stimulation poles 38 can be selected to recapture thenerve 42 if necessary without requiring further physical manipulation ofthe lead 36 after insertion, thereby reducing the potential forinfection and improving device usability. Put another way: the spacingof electrodes 38 along the lead 36 ensures that electrical communicationbetween the lead 36 and the phrenic nerve 42 is maintained by allowingany of the four pole to be energized. Four poles were chosen based uponminimizing cost and complexity of the electronics but the design willalso work just as well with 5, 6, 7 etc. poles. Thus, even if theposition of the lead 36 has shifted as a result of patient movement orother factors two of the four poles 38 will always be in sufficientproximity to the phrenic nerve 42 to allow for stimulation to occur. Anycombination of leads, surface area, distance between electrodes and leaddiameter can be envisage that would optimize the stimulation ability ofthe lead to excite the phrenic nerve.

It is expected that a single pair electrode sites will be closest to thephrenic nerve and that the pair of sites that best stimulates the nervewill be found experimentally in each instance. Both unipolar and bipolarstimulation regimes are contemplated with both anodal and cathodestimulation available for the therapeutic use. Both monophasic andbiphasic stimulation are contemplated but it is expected that biphasicstimulation from a single pair of well-placed electrode poles will beoptimal and result optimal stimulation and minimal nerve damage. Chargedensities greater than 30 μC/(cm² phase) have been shown to cause nerveand tissue damage and software and hardware protection mechanisms areenvisaged to ensure this limit is not exceeded.

Given a number of different leads and stimulation devices may beattached, the lead 36 is given a specific resistor value (selectionresistor) accurate to 5% or less to identify the lead to the S/C. Themore accurate the selection resistor used the greater the number ofleads that can be distinguished. For the purpose of giving an example a1% accurate resistor will be used. Such resistors are commerciallyavailable and very low cost. The resistor is used to identify the leadtype attached in terms of the number of electrodes available, theelectrode surface area and may be used by software and hardware to limitthe charge density based upon lead surface area. This allows thesoftware and hardware to ensure the charge density for the attachedelectrode is not exceeded and minimized the potential for user error.

As is shown in FIG. 2a , the resistor 39 may be embedded into the lead36 and can be read after connection. In a similar fashion a resistor maybe associated with each electrode in the lead or associated with eachelectrode pair in the lead to provide location information to the S/C.The benefit of using a separate pair of connector terminals formeasuring the resistance defining the lead type attached is that theresistance can be measured independent of any errors created byimmersions of the in fluids or body tissue. Each resistor value must bedistinguishable for all other resistor values used in other leads suchthat the values do not overlap in terms of the resultant measurementaccuracy and is used to determine which probe is attached. Overlapbetween two distinct resistors values in terms of measurement rangewould cause confusion in the distinction between leads. To avoidpotential issues with misreading the lead type attached, the measurementaccuracy must be significantly less than the difference between theupper and lower ranges of the two closest resistor values. Thisdifference should be large or the measurement accuracy must be high.

FIG. 2b shows how the selection resistor 39 could be used to determinewhich electrode is active. In this example Vcc drops across the resistordivider R1 and R2 and is measured by an ADC (Analog to DigitalConvertor) 50 at the junction of R1 and R2. This example is given forillustration purposes only and in reality ESD protection and currentlimiting resistors would be used to prevent damage to the stimulatorduring use. For instance, R2 could be embedded within the lead and R1could be internalized.

With a 1% accurate resistor, using a resistor divider with the requiredESD protection, this system could easily accommodate 10 differentconfigurations of electrodes without any potential for lead recognitionerror and accurately identify the electrode attached with a 10 bit orgreater ADC (1024 bits). Assuming the R2=10K and R1 has a range of 1K to500K and Vcc the input voltage is 5 volts, then range would be quitelinear between 0.5 and 3.0 volts. The actual resistance values for R1and R2 can be optimized based upon the actual system requirements. Lookup tables with allowable voltages drop variances could be used todetermine which lead type is attached. If the voltage is between x and ythem probe z is attached.

The voltage variance is a function of supply voltage variation, resistorvariation, electrical noise, ADC error etc. One skilled in the art ofworst case error estimation can easily account for these potentialvariations using a worst case analysis or independently measuring thesupply voltage and accounting for this error.

Other methodologies using resistors in conjunction with 4 or morecomparator circuits (one more than the number of circuits required to bedistinguished) could also be used to produce a digital output whichwould go high or low to denote which lead was connected but this wouldbe less flexible and cost more. Other approaches such as using embeddedRF ID tags within the lead are also possible but these typically costmuch more and are subject to proximity issues, plus the detection ofswitching leads and making this detection becomes more problematic. Aserial memory device using an I2C interface could also be used where aserial number denoting the specific lead attached along with pertinentparameters eliminating the need to update software if new leads areadded to the product portfolio. Such a system while beneficial iscomplicated with the requirements of ESD protection. The benefit of theresistor approach is new probes can be added robustly, cheaply anddistinguished by the system without the requirement for adding activecomponents to the lead.

Another approach would be to use a serial memory device such as a SerialElectrically Erasable and Programmable Read-Only Memory (EEPROM)organized as 128 words of 8 bits each. Each EEPROM could be programmedwith its own unique identification number and could also be programmedwith the allowable setting limits or product specific features such aselectrode surface area and number of electrodes. The EEPROM could alsobe used to store current settings. Thus, if a new stimulator wasconnected to a lead or the leads were switched on an existingstimulator, the stimulator device would automatically recognize the leadwas changed after reading the data in the EEPROM and update deliveredstimulus parameters in accordance with those data stored, such as in theform of a lookup table, etc. within the stimulator/controller 12 andaccessible by CPU 31. Separate resistor values could also be used todistinguish left and right stimulation leads eliminating the requirementfor the user to know which connector to attach to which lead. This is ofparticular issue in the ICU and eliminating the requirement for tracingleads after initial setup and disconnection would also reduce thepotential for user misuse. Attributing a set of parameters to a specificlead would only be done after setup. After setup, the set of parametersattributed to a specified resistance would follow the specificresistance measured. The use of such resistance can also be used todefine which functions in software to provide. For instance, specificleads used only during setup can be used to minimize functionality basedupon the recognition of the measured resistance denotes that a setuplead is being used and that therapy functions would be disabled for thislead.

Based on the above description is should be understood that the system10 functions by sending an electrical pulse via the pulse generator 32as determined by established values determined by the system or input bya user to the CPU 31—to the leads 36 (via lead cables 34) so as tostimulate the phrenic nerve of a patient 22 in manner sufficient toactivate the musculature associated with lung function (either or bothsides of the diaphragm 20). The level of stimulation will occur withinbounded values of a stimulation waveform in terms of current, currentdensities, charge densities and voltage as determined by thestimulator/controller 12, CPU 31, etc. In FIG. 2c the electrode couplet1-2 at location provides more work by the patient than electrode couplet2-1 seen at location 35. This is generally true but some level ofproportionality appears with current levels supplied to the lead. Asseen at location 39 and 31.

The stimulation may be to both the left and right phrenic nerve and thusbe bilateral or unilateral, while the resultant effect of stimulation onthe diaphragm may be bilateral or unilateral as well.

In some embodiments a purpose of the stimulation regime is to causesufficient activation of the muscle to cause a training effect on themusculature. Muscular train at level sub maximal are believed to providea therapeutic benefit and to aid in weaning patients from mechanicalventilation more quickly than is otherwise possible. Effectiveness ofthe level of any given stimulus will be determined by observed patientwork in a sedated patient whose respiratory function is partially orentirely supplanted by mechanical ventilation.

The level of muscle activation required to induce the desired trainingeffect may be below the level required for gross motion of the diaphragmand lungs in a normal healthy patient. When a patient has abnormalrespiratory mechanics the work required may be significantly higher forthat patient than a healthy person. For this reason, medical judgmentwill be required to target a work or power expenditure suitable for thetherapy. It is expected that the physician will target a nominal work orWork-of-Breathing (WOB) value that is in the range of expected power fora healthy normal patient. This work or power level will be a referencepoint and used to titrate the level of stimulation. It also possibleonce a target level of work is determined by the clinician, thestimulator could automatically increase the level of stimulation basedupon a level of work desired based upon a feedback loop of work measuredwithin bounds set by the clinician for a maximum allowable currentamplitude, frequency of stimulation etc.

The periodicity of the electrical stimulation may vary over a wide rangeand it may be delivered in synchrony with natural ventilation.

However, before any such stimulation may occur, the phrenic nerve (rightand/or left) of the patient 22 must first be located and accessed.

Turning now to the insertion of the lead 36 may be accomplished by avariety of techniques, an example of one being shown in the sequence ofimages depicted in FIGS. 7-10.

Before lead insertion, the patient 22 is intubated and sedated, or morelikely already in this state due to the presumption of requiringmechanical ventilation. The patient is in supine position (lying flat)with head turned to the contralateral side.

Identification/location of the phrenic nerve is performed using ahandheld stimulator 44 and ultrasonic probe at the level of the cricoidcartilage and lateral of border of the sternocleidomastoid muscle (SCM)approximately at the level of the C5 vertebra such as in the mannershown in FIG. 7. The patient is first assessed to determine suitabilityfor lead insertion. Ultrasound is used to determine the patient anatomyis suitable for lead placement and the hand held stimulator is used todetermine that the phrenic nerve is functional and capable ofstimulating the diaphragm. Once the patient has been accessed assuitable for treatment, the lead insertion site identified, the areaaround it is cleaned and sterilized. A small incision 46 is made at thedesignated access site with a scalpel or other cutting instrument.

With ultrasound guidance, a cannula 48, such as a Pajunk® Touhy needleshown in FIG. 1b , is inserted into the initial incision site. The Touhyneedle is a monopolar needle with an insulated shaft with only the tip49 being electrically conductive and in communication with thestimulator/controller 12. This allows for localized nerve stimulation atthe tip 49. The needle 48 is attached to the stimulator 12 via anextension lead 51. A second electrode 53, shown in FIG. 7, is connectedto the patient's skin and to the extension lead to create a return pathfor the electrical stimulus. This extension lead 51 contains a resistorthat identifies that the setup needle 48 is attached and that the needleinsertion process is underway. The user is now given the ability tostimulate the needle 48 via the stimulator/controller 12. The software(not shown but should be considered a component of the CPU 31 shown inFIG. 1a ) in the stimulator recognizing the unique resistance of theextension lead 51 for the monopolar needle 48 switches to a nervefinding programs which differs from the e pacing function discussed ingreater detail below.

Once the needle 48 is advanced beyond the skin insertion site, theneedle is advanced parallel to the muscle fibers of the anterior scalenemuscle (ASM), and under the sternocleidomastoid muscle (SCM)(illustrated in FIG. 3) with the tip of the needle 48 just distal to thephrenic nerve 42. Stimulation can be used to induce a hiccup like actionof the diaphragm and let the operator know that they have identified thecorrect nerve under ultrasound guidance. This stimulation can be limitedto being performed during inspiration period utilizing the flow sensorto distinguish between inspiration and expiration such that diaphragmcontraction is in synchrony with the breath phase of the ventilator.This prevents auto-triggers on the ventilator and minimizes thepotential for barotrauma and auto PEEP.

Note that if at any time collateral e.g. brachial stimulation isobserved (as noted by corresponding arm movement with stimulation) thenthe cannula 48 is repositioned approximately 1 cm caudally. Thestimulation process is then repeated at the new location untilcorresponding diaphragmatic movement is noted without collateralstimulation.

Once signal capture is achieved the needle is advanced to transverse thephrenic nerve 42 under ultrasound guidance such as in the manner shownin FIGS. 7-8. A multipolar lead 36 is inserted through the monopolarneedle 48, such as in the manner shown in FIG. 8. The position of thelead tip 37 (see FIG. 2a ) is observed by ultrasound and is positioneddistal to the tip 49 of the cannula 48. Once the lead 36 is properlypositioned (such as is shown in FIGS. 3-4), the cannula 48 is removedfrom the patient 22 in the manner shown in FIG. 10. The multipolarneedle/lead 36 is designed such that both ends will fit through themonopolar needle 48 facilitating the needles removal. A stylet may beused to strengthen the lead during insertion into the needle.

The lead housing 35 may be flexible to maximize comfort and the axis ofthe lead 36 will form an angle with the axis of the body of the phrenicnerve 42. Both orthogonal alignment (an example of which is shown inFIG. 8) and substantially parallel alignments (an example of which isshown in FIG. 9) are contemplated with the included angle varying fromabout 90 degrees to 0 degrees.

Next the lead 36 is connected to the handheld stimulator 44 anddiaphragmatic movement is verified. There are six possible combinationsto tests as outlined in FIG. 2a . The operator uses the defaultstimulation parameters provided by the stimulator/controller 12.Stimulation will be delivered in synchrony with the inspiratory cycle ofthe ventilator at the operator's request. The operator may quickly gothrough the combination of stimulation poles by testing the variouscombinations over a number of breaths. This could be shown graphicallyto the operator in terms of work for a given electrode pair similar in abar chart form making the distinction of best pair easy for theoperator. The level of work induced by the stimulator may be averagedover a number of breaths. Stimulation parameters may also be increasedif diaphragm movement is not seen or measured. As stimulation parametersare adjusted this could also be shown graphically by adding bars to thebar chart for the specific pair allow the operator to see thedifference. The measurement of WOB, which is described below, iscritical to finding the optimum pair of poles for stimulation. Ifmovement cannot be verified in terms of patient WOB during electricalstimulation, then the procedure is terminated.

Assuming however that the process is successful and diaphragmaticmovement is confirmed, the process is repeated on the contralateral sideto thereby implant a lead 36 at both the right side and left sidephrenic nerve.

It should be recognized by one of ordinary skill, that the above processprovides notable benefit in that this technique avoids any inadvertentvascular-neuro-pulmonary injury that more invasive surgical techniquesor implanted devices may cause.

In addition, lead 36 is free to move along the insertion path if thepatient 22 is repositioned. Since such movements will be initiated bythe clinician, adjustments to optimal stimulation pairs can be performedif the clinician recognizes a reduction in the work of breathing(discussed in greater detail below) after a positional change. Also, andas mentioned above, the primary purpose for using multiple poles in eachlead 36 ensures that at least one electrode pair will still cross thephrenic nerve before and after any repositioning of the patient.

System Operation Description with the Lead

With the lead structure and the technique for locating and accessing thephrenic nerve of the patient well described we turn to the operation ofthe electrode selection methodology. Lead insertion results in the axisof the lead body lying across the nerve bundle of the phrenic nerve,such as in the manner shown in FIGS. 3-6. A pair of the electrodes willlie closest to the phrenic nerve 42 and the stimulator/controller 12finds that pair by stimulating sequential pairs of electrodes (two ofelectrodes 38 a-e) during selected breaths while looking at the work orpower generated by that breath as measured from the pressure history atthe wye sensor 14. In general, the maximal work for the minimalstimulation current will correspond to the best electrode pair. Thisprocess can occur automatically or directed by the userphysician/technician (not shown). The level of work or power for eachstimulus pair may be assessed over a number of breaths and compared tothat exerted by the other pairs of poles. The maximum respiratory powermeasured for a given level of stimulation of the pair of poles wouldthen represent the optimal pair. Since the lead 36 is not firmlyanchored it can move and the best electrode pair may change with time orrepositioning of the patient. This process for searching for the optimalpair may be initiated upon request by the operator or could be initiatedautomatically based upon a level of the patient work dropping below aspecific level. See for example the change in lead positions depicted inFIGS. 5 and 6. In FIG. 5 the lead as inserted may have moved or beenmisaligned relative to the phrenic nerve due a patient positional changebut given the flexibility of selecting the lead stimulation poles 36 andthe system 10 the clinician may easily adjust the lead stimulationpoles. This change in optimal poles is illustrated in FIG. 6 where theoptimal poles change from 1 to 2 to 0 to 1

Stimulation optimization will likewise compare the work or power of abreath as a proxy for evoked response of the diaphragm. The stimulationmay occur at any parameter set within bounds defined by the inputparameters on the GUI 33. In general, the clinical user will look forstimulation parameters within these limits that maximize work or powermeasured for the breath.

It is anticipated that the GUI 33 will have one control for stimulationlevel with detailed parameters set a priori and a display of work/powerof the stimulated breath. The user will exercise medical judgment insetting stimulus for a given observed work/power of the stimulatedbreath.

System Operation Description with the Wye

As described in connection with FIG. 1a the pulse generator 32 withinthe stimulator/controller 12 delivers electrical stimulation to at leasttwo electrodes or a pair of electrodes (two of electrodes 38 a-e)selected from all available electrodes on lead 36. One of the electrodepair is the cathode and the other electrode is the anode for bipolarstimulation. This bipolar stimulation is one embodiment. It should beunderstood that unipolar stimulation with a remote indifferent electrodeis also contemplated within the scope of the invention. The electricalstimulus will have at a minimum an adjustable number of breaths betweenstimulation breaths, repetition rate, a current amplitude, a pulsewidth, and a pulse train waveform. The values of these parameters may beset by the user through interaction with the GUI interface 33 ofstimulator/controller 12 separately for both pacing leads. Theseelectrical parameters may vary over a range and it is expected that manyor most will be set automatically as set forth below. Other inputparameters required for system operation are patient lung compliance anda patient lung resistance. These can be measured by the ventilator orusing the stimulator and entered by the user via GUI interface 33. FIG.19 is a table showing the parameters for the GUI and the set labeled 900will be input parameters (13 on FIG. 1a ) that will set by the user. Theparameter space labeled 902 in FIG. 19 is expected to be displayed onthe interface 33 screen. The parameters 904 will be input by the user aswell as these are required for the work and power measurement process.These are typically measured by modern mechanical ventilators and may beentered from there. These values can also be estimated from knowledge ofthe patient and their state of health.

In operation, the stimulator/controller 12 will count patient breathsbased on wye pressure and wye flow communicated via sensor cable 28 fromthe instrumented wye (wye sensor) 14 to the stimulator/controller 12.Although the stimulator/controller can be set to interact with each andevery breath, it will normally select a single breath from a sequence ofbreaths herein after referred to as the selected breath. A simple ratiois used and in the various figures both a one of two (1:2) and a one ofmany ratio (1:N) are shown for the selection criteria. The selectioncriteria mean that both the following or subsequent breath will bemechanical ventilator controlled and the preceding or predecessor breathwill be mechanical ventilator controlled. The immediately precedingbread is hereinafter referred to as the predecessor breath while theimmediately succeeding breath after a stimulated selected breath iscalled a successor or subsequent breath. When referring to either ofthese two breath types the term “companion breath” is used. The animaldata presented in FIG. 18 shows a 1:3 stimulation regime and this animalwork suggests that a ratio of 1:2 to 1:8 may encompass a workabletherapeutic range for a human patient.

The human breath has an inspiratory phase characterized by a positiveflow of air through the wye into the patient, and an exhalation phasewhich begins when wye flow drops below zero and turns negative as thepatient exhales the volume just inspired. This end inspiratory eventbegins the outflow portion of the breath cycle. In operation, thestimulator will deliver the electrical stimulation starting with theinspiratory phase when flow exceeds a predetermined level and endstimulation at the start of the exhalation phase when flow drops below apredetermined level, this stimulus will occur only during the selectedbreath. Since the stimulation is not continuous for each inspirationthere will typically be a predecessor mechanical ventilator breath and asubsequent breath. The selection of a breath is a simple ratio. That isselected breaths may occur every other breath (1:2) to any arbitraryvalue say one selected breath every 20 breaths (1:20). It is expectedthat a ratio of 1:4 or so will provide adequate treatment for VIDDhowever this will need to selected based upon clinical practice.

The work and power measurements are made based upon the respiratoryequation of motion. Although unnecessary for a qualitative indication ofwork or power it is best to convert measurements to a uniform standardand the patient work level or power expended in a breath is reported asthe Work-of Breathing (WOB). This convention reduces the necessity toconvert units and the like. The equation of motion used to calculate WOBis the same equation used to set the target pressure level based uponthe proposed level of support in Proportional Assist ventilation (PAV)mode of ventilation, which is a spontaneous mode of ventilation. Theventilator may be used to assess the patient's compliance and resistancebecause it dictates when respiratory mechanics maneuver can be initiatedand the resultant compliance and resistance measurement values will thenbe used to determine the WOB for the patient. The user will need totransfer the ventilator measured compliance and resistance measurementsmanually from the ventilator to the PEPNS console. It will be necessaryto perform respiratory mechanics periodically but unlike PAV, thepotential for runaway does not exist. In theory if the patient does notmake a voluntary inspiratory effort during a mandatory breath or thePEPNS System does not electrically stimulate the diaphragm, the WOBshould be zero joules/L. Work is normally measured in Joules butdividing by the volume allows the level of work to be normalized againsta unit volume. The equation of motion equation should predict the wyepressure accurately and when the measured wye pressure matches thepredicted wye pressure it indicates that there is no patient effort andthus no WOB. A difference will occur in the predicted and measured wyewhen the diaphragm is stimulated and these will be attributed todiaphragm effort.

The benefit of this approach is that the WOB can be assessed in relationto the level of work a normal healthy patient exerts during breathing atrest. Normal WOB has been reported in the literature to be 0.3 to 0.5J/L in healthy children, adolescents, and young adults. Certain diseasestates that increase lung resistance and compliance dramaticallyincrease the level of work a patient has to exert to breath so basingthe level of work on a pseudo WOB measurement such as a reduction in thepressure time product (PTP) could mean that a sick patient is working atsignificantly higher levels than a normal healthy person at rest. UsingPTP as a proxy for work is not workable in a clinical setting as it maygreatly overestimate or underestimate patient work resulting inextremely inappropriate stimulation levels. This is not the purpose ofthe PEPNS system (over exertion of the diaphragm) a method to assess andprevent this from occurring is disclosed. Allowing the clinician toadjust the stimulation level based upon a known measurement of WOBallows the physician to titrate the level of effort based upon clinicalassessment. Feedback does not exist to set this desired level of WOB,this is the physicians decision based upon a myriad of inputs that willbe unknown to the stimulation device, disease state, age, weight,temperature, heart rate, end tidal CO2, metabolic rate etc. Once a levelhas been set by the clinician feedback could be used to maintain thedesired level. Use of this WOB measurement will help minimize thepotential for inducing diaphragm fatigue due to overstimulation whichcould happen when blindly setting a stimulation level withoutunderstanding the underlying respiratory mechanics and level of workbeing induced. Examining diaphragm motion is like looking at a machinelifting a weight. Knowing the acceleration or velocity of the weightgives no idea of how much work the machine is performing. Knowledge ofthe weight is required and this is comparable to knowing the patient'scompliance and resistance.

The equation of motion for respiration will be used to estimate thepatient WOB in an electrically stimulated breath. In a breath withoutelectrical stimulation the WOB should be 0 J/L because P_(mus) will be 0cmH₂O.

According to the equation of motion for the respiratory system:P _(vent) +P _(mus)=elastance×volume+resistance×flow

Where elastance a measure of the tendency of a hollow organ to recoiltoward its original dimensions upon removal of a distending orcompressing force. It is the reciprocal of compliance. Resistance orAirway resistance is the opposition to flow caused by the forces offriction. It is defined as the ratio of driving pressure to the rate ofair flow.

Elastance is measured in cmH₂O/Liter, volume in Liters, resistance incmH₂O/Lpm and flow in Lpm. P_(vent) is the pressure exerted by theventilator and P_(mu) is pressure exerted by the diaphragm muscles andboth are measured in cmH₂O.

This equation can be rearranged to show:P _(vent) +P _(mus)=elastance×volume+resistance×flow+PEEPP _(mus)=elastance×volume+resistance×flow+PEEP−P _(vent)

Where P_(vent)=P_(wye)Work=Pressure×VolumeWork=∫₀ ^(Vt) Pmuscles*dV (joule)

Where dV is the rate of change of volume and Vt is the tidal volume ofthe inspiration. This can also be expressed as:Work=∫_(t0) ^(t1) Pmuscles*Qdt

Where Q is the instantaneous flow, t₀ and t₁ are the start and end ofinspiration.WOB=Work/Liter=Work/Vt (joule/Liter)

Most ICU ventilators are capable of measuring respiratory mechanicsproperties such as static and dynamic compliance and resistance. Sincethe WOB will be primarily used to gain an understanding of the level ofeffort that electrical stimulation is creating small errors inmeasurements will not be of consequence unlike the accuracy requirementsneeded for compliance and resistance measurements needed for modes ofventilation such as Proportional Assist Ventilation. In use thephysician user will input measured or estimated lung compliance and lungresistance measures in to the GUI. It is also possible with the sensorsat the wye, the wye flow and pressure to assess the patient'srespiratory mechanics. Currently for simplicity these measurements willbe made independently but they the PEPNS system is capable of makingthese measurements during ventilation.

The flow sensor and wye pressure sensors can be used to measure Pvent(Pwye) and flow at the wye, Qwye directly. Volume accumulation may becalculated by integrating the Qwye as the breath progress beginning atthe start of inspiration and ceasing at the end of inspiration.

The Operator can enter values for compliance and resistance into thestimulation device via the GUI and update these values when they havebeen deemed to change significantly. The stimulation device could alsocommunicate directly with the ventilator and eliminate the need for thisdata entry and get the values directly from the ventilator.

The benefit of this method of calculation for work is no data onprevious breaths or breath types is required. The measurement inindependent of the previous breath type and no knowledge of the previousand current breath are required. In contrast PTP as a pseudo measurementof WOB will only work if the same breath type are compared between astimulated and unstimulated breath.

Turning to FIG. 11, there is shown a set of waveforms with the same timescale 108. A flow channel 100 is shown with the simultaneous signal ofthe pressure channel 102. Both the pressure and flow measurementsreflect the values at the wye 14 and these are reported to thestimulator/controller and form the wye pressure measurement and wye flowmeasurement referred to later in the description. Also seen in thefigure is a waveform panel 104 showing the electrical stimulationsupplied to lead system 116 from the pulse generator 32. A calculatedvalue 122 is shown as the waveform 106 and it is labeled work in thefigure but it reflects both observed work as well as power delivered bythe patient into the system, as explained in detail later.

In FIG. 11 the selected and stimulated breath generally designated 110commences at time T=1 with an inspiratory phase indicated by the rapidrise in flow at 114. This is a flow control breath denoted by a constantflow and the resulting pressure being a function of the compliance,resistance and diaphragm effort of the patient. This inspiratory flowstarts the delivery of the stimulus at 116 in the figure. When thepatient's exhalation begins at 118 the stimulation ends at point 120.During the inspiration duration from event 114 to event 118 the pressurein the wye is compared with a predicted and modeled pressure in the wye.This pressure difference is called Pmus and it reflects the pressurecomponent of the work done by the patient's muscle. Pmus along withother parameters is used to compute the value of work and power seen inchannel 106 as work/power waveform 122. Basically the wave form envelopeis the instantaneous work performed and the area bounded by the waveform122 is the power expended by the patient 22.

Turning to the previous or predecessor breath 112 we see a anothermechanical ventilator breath in a flow control mode. At time T=0 thebreath starts and the patient experiences a rapid delivery of flowsymbolized at infection point 124. The pressure rise is set by themechanical ventilator and is represented in the figure as slope 126.Since this is not a stimulated breath the Stim Signal channel is emptyand since the predicted value of Pmus and the measured value at the wyeare identical they add to zero and this term in the work/powerexpression is zero so the work value computes to zero and nothing or nowork is shown in the work channel 106.

FIG. 12 follows the same format as FIG. 11 but in the interest ofclarity the timing synchrony lines are not shown. In this breathsequence a predecessor breath 200 is followed by a selected stimulatedbreath 202. The pressure controlled breath 200 begins at time T=0 withthe rapid pressurization to the plateau 208. This corresponds in theflow channel 206 with the rapid rise in flow at event 210. At time T=1the mechanical ventilator has met its inspiratory time requirements andthe pressure drops and the flow goes negative as the inspiratory phaseends and the expiratory phase begins. After the mandatory breath periodexpires the ventilator delivers another mandatory breath and theinspiratory flow detected at the wye 24 causes the console to turn onstimulation seen as stimulation train 212. In this pressure controlledbreath the pressure level is also set to the same pressure level andboth breath 200 and 202 have reached the preset pressure shortly afterT=0 for breath 200 and shortly after T=3 in breath 202. During thesecond mandatory breath 202 the stimulation causes work of the patientwhich increased the flow into the lungs as seen by comparing height 214with 216 in the figure. The pressure remains constant between becausethese are pressure controlled breath. If Pressure Time Product (PTP)methodology was used as a method of determining WOB there would be nodifference in work measured yet the effect of stimulus can be seen inthe differences between resultant flow. The conventional PTP proxy isblind to obvious increase in patient work while the inventive anddisclosed methodology shows an accurate measure of work at waveform 218.This point is shown on the figure by the lack of a work waveform atlocation 220 corresponding to time T=0 on the figure.

FIG. 13 shows the operation of the invention in the context of a morecomplicated Synchronized Intermittent Mandatory Ventilation (SIMV) modein a flow control regime. SIMV is used as a transition mode where theclinician is able to set a minimum number of breaths per minute andaddition breaths taken by the patient will result in a spontaneousbreath being delivered. The most common form of a spontaneous breath ispressure support ventilation which is both initiated and terminated bythe patient. The mandatory breaths may be ventilator initiated orpatient initiated. There are four breaths in the FIGS. 300, 302,304 and306. The first breath 300 is initiated by the mechanical ventilator andshows a flow control breath, similar to 112 in FIG. 11. It precedes thesecond breath 302 which a spontaneous breath. In this example breath 302is a selected breath so it will invoke stimulation of the stimulationlead because the console will have no knowledge of the type of breathabout to be delivered it is critical that the WOB measurement isindependent of the breath type and any knowledge of the preceding breathtypes. This is also a patient initiated breath and in this case aspontaneous breath. The inspiration starts at the inflection point 308in the flow channel 310 which starts the stimulation 318 in thestimulation channel 314. The pressure measurement from the Wye 14 istaken as the Pwye measurement which is used to calculate the presence ofand the value of the work and power of the patient in breath 302 as afunction of the difference between the measured and predicted wyepressure. In accord with the SIMV modality the next breath 304 will be amandatory breath since in our example it is not a selected breath itwill not be stimulated and it will be similar to breath 300. After somedelay indicated by the line break in the channels another mandatorybreath occurs in this example it is a selected breath and therefore astimulated breath. In this breath, the machine initialed flow event atinflection point 320 starts the stimulation 322 in the stimulationchannel 314. Once again, a work and power measurement can be made anddisplayed as seen by waveform 324 in the work channel 316.

It is important to note the predecessor breath 300 and the subsequentbreath 304 are essentially identical except for their timingrelationship to the selected breath 302 and 306, that is breath 304 isboth subsequent to breath 302 and a predecessor breath to selectedbreath 306. For this reason, the un-selected predecessor breaths orsubsequent breaths are called “companion breaths”.

FIG. 13 also shows no measured work for the companion breath 300 atlocation 326 and no work for the companion breath 304 at location 328.While the selected stimulated breaths show patient work in the workchannel at 324 and 330 respectively. The duration 332 of stimulation ofselected breath 302 is initiated and terminated by the patient while theselected breath 306 is both initialed and terminated by the mechanicalventilator 30 resulting in differing waveforms for work as seencomparing work waveform 324 with work waveform 330. The figure shows thecompatibility of the system with SIMV ventilation modalities.

FIG. 14 shows the operation of the invention in the context of a morecomplicated Synchronized Intermittent Mandatory Ventilation (SIMV) withpressure control as the mandatory and pressure support ventilation (PSV)as the spontaneous mode. There are four breaths in the figure 400, 402,404 and 406. Breath 400 is a mandatory breath and breath 402 is aspontaneous breath in PSV and it is a selected stimulation breath. Inthe figure the flow initiated stimulation begins at 408 and ends at 410.The duration of stimulation is patient driven and is the consequence ofa patient initiated inspiratory phase and the cessation of stimulationis triggered by a patient initiated exhalation at point 412. After sometime, a second selected breath occurs and it is a machine initiatedmandatory breath with the beginning of stimulation at 414 and end ofstimulation determined by the mechanical ventilator at location 416. Inthis case it was preceded by a PCV mandatory breath 404. Once again onlythe stimulated show an actual work measurement at locations 418 and 420for selected breaths 402 and 406 respectively. In this example thesystem is integrated with pressure controlled and pressure supportedmodalities where pressure time product measurements will not work.

FIG. 15 shows the operation of the system in a bi-level ventilatortreatment modality. In this mode two post expiry pressures PEEP hi andPEEP lo values are set on the mechanical ventilator 30. These may betens of cmH20 apart in pressure. There are six breaths shown in thefigure. Using a one in two ratio (1:2) for selecting breaths. Breath 500breath 504 and breath 508 are selected stimulated breaths. While thepredecessor or subsequent, companion breaths 502 and 508 are driven bythe mechanical ventilator 30. Note that the system gives work measuresat locations 512, 514, and 516 respectively for the selected breaths500, 504 and 508. Note as well that the pressures and flows betweenthese selected and stimulates breaths vary dramatically as representedby the corresponding waveforms in the pressure channel 520 and the flowchannel 522. Using the work and power methodology relying on Pmus or thedifference between predicted and measured wye pressure Work iscalculated in a sensible way and the largely different pressure and flowtraces are accommodated. An alternative Pressure and Time Productestimation of work is unable to provide reliable and accurate measure ofwork and power where the pressure at the wye is integrated andsubtracted from the preceding wye pressure. As can be seen from theprevious ventilator modalities in FIG. 11 to FIG. 15 the inspiratorytime and breath type may vary significantly between breaths. It isgeneral true that any estimation of work based upon a comparison of twobreaths even if the breaths are of the same type is unworkable in manysituations which can arise, and are exemplified by the FIG. 6 waveforms.

FIG. 16 shows the system operating in a pressure regulated volumeventilation modality where both pressure limits 608 and flow limits 610are set for the mode by interaction with the mechanical ventilator 30.This figure shows a 1:2 selection ratio with breath 600 and 604receiving stimulation, and companion breath 602 controlled by theventilator This pressure regulated and volume regulation mode limitsboth pressure and flow as seen with breath 602 inspiration event 612rapidly reaching the limit shown as 610. As well as reaching thepressure limit a short time later indicated by reference numeral 614.Even in this mode the work and power measurements seen at 618 and 616respectively for selected breath 600 and selected breath 604. Once againthere is no reported work the machine breath 602, even when the machinebreath 602 is operating at limit conditions.

Work/Power Measurement

FIG. 17 A and FIG. 17 B should be considered together. FIG. 17A is adiagram of a sequence of breaths that was generated by a computer modelof a patient coupled to mechanical ventilator via a patient circuittubing operating in a volume control mode and then in a pressure controlmode. The numbered breaths 700,704,708,712,716,720,724,728,732, 736,740seen in the pressure channel 746 are all selected stimulated breathswith the selection criteria ratio being 1:2. The remaining companionbreaths are predecessor or subsequent breath driven by the mechanicalventilator. Breath group 742 in the flow channel 748 are all volumecontrolled breaths VCV and the remaining group 744 in the flow channel748 are all pressure controlled breaths.

The patient compliance and resistance were modeled to be 100 ml/cmH2Oand 5 cmH2O/Lps respectively. The patient circuit tubing compliance wasset to 2.5 ml/cmH2O.

Channel 750 represents the pressure time product of each breath. It isconventional to compare the pressure time product 754 of a breath saybreath 740 with the pressure time product 756 of a predecessor breathsay for example breath 738. In the table at breath 740 the pressure timeproduct difference is −10. In conventional practice this value would betaken at the work of breath 740. However, we know this is a stimulatedbreath and the patient work is not negative. Work channel 752 using thepreviously described process the work 756 is shown as a positive valuereflecting the actual patient work performed. The figure shows theinadequacy of using pressure time products of two breaths. FIG. 18 showsactual data taken from a sedated pig. The pig was heavily sedated tocompletely suppress natural respiratory drive. The pig was otherwisehealthy and normal not presenting a complicated disease state. It wasobserved over the course of several hours that the diaphragm becameweaker. At 1:3 selected breath ratio was selected and the pig stimulatedat a level reflecting healthy normal work of breathing. In comparisonwith a control the measure work of breathing (not shown) was consistentbetween breaths the stimulation protocol reflected by stimulus 800 forselected breath 802. Repeated periodically on a 1:3 selection basisimproved and persevered diaphragm function. To the investigators thissuggests that selection ratios above 1:2 are beneficial and that anoptimum may be found for clinical practice. In the experimentaccelerometers were placed on the diaphragm and the waveform complex 804and 806 reflect capture and effective stimulation at the parametersselected for stimulation.

FIGS. 19A, 19B, and 19C is a table showing the input parameters for theGUI.

Certain setting such as group 900 may be directly set by the user whilegroup 904 will need to entered manually. Group 902 represents theexpected waveform data to be presented to the user.

Risks Associated with Therapy

There are a number of risks associated with the therapy. The FIG. 20Aand FIG. 20B present these risks in a tabular format with associatedalarm conditions. These risks may result from user misuse or from afault condition in the system. For instance, electrical stimulation mayoccur for too long a period if there is water in the patient circuit andit tricks the PEPNS system into thinking the patient is continuouslyinhaling. Water may offset one of the differential flow sensor pressurelines resulting in what looks like a continuous flow. Such an issuecould also occur if the wye becomes disconnected and the ventilatorcontinues to deliver flow until the ventilator detects that a disconnecthas occurred. Water in the circuit may also cause auto trigger resultingin a high respiratory rate. Water in the circuit can causes a sloshingmotion that results in air flow moving forwards like it does duringinhalation and reversing as the water wave reverses simulating anexhalation. This motion may be misinterpreted by the ventilator as apatient effort resulting in the ventilator falsely triggeringinspiration. The user may also forget to connect the flow sensor and wyesensor at the wye during suctioning of the patient resulting in thePEPNS system, failing to deliver electrical stimulation because the wyesensor is no longer connected to the wye. Also, if the patient'srespiratory mechanics changes, there exists the potential that thepatient will increase their level of work or reduce their level of workoutside a level desired by the physician. Alarms already exists inpacing devices for lead impedance and device failures due to overcurrent. Providing stimulation in conjunction with ventilation creates arequirement for additional safety measures to bring the user's attentionto erroneous conditions. There exists a need to bring these alarmconditions to the user attention and to prevent erroneous electricalstimulation. The following alarms shown in FIG. 20A (A, A1 and A2 to beviewed as a continuity) and FIG. 20B have been implemented to preventsuch conditions. The following headings are shown in the table:

Alarm Name: Name of alarm displayed to user.

Detection Criteria: criteria used to detect the alarm condition.

Description: Description of what the user is instructed to do when thealarm condition is detected.

Alarm Reaction: The PEPNS system reaction to the alarm. Uponannunciation of the alarm, the PEPNS system may enter a safe state wherethe drive to the electrical output is disabled or the device maycontinue operation. The reaction chosen is a function of the residualrisk to the patient.

Enable/Disable Alarm: User has the ability to enable/disable specificalarms as part of device if the alarm condition is duplicated on theventilator. For instance, most ventilators will have an apnea alarm andthis alarm will only need be invoked if the ventilator does not havesuch an alarm. Duplicating alarms will cause user frustration so givingthe ability to disable these alarms will greatly improve usability ofthe device.

Name/Units: This section describes the units in which the alarm is set.

Range: This section describes the range of the alarm setting.

Giving the user the ability to detect changes in patient effort allowsthe user to detect loss of stimulation or changes in patient respiratorymechanics. The risks exist that the patient's respiratory mechanics maydeteriorate after the initiation of therapy as a result of the diseaseprogression, alerting the user to these conditions and not casing thepatient to overexert the level of effort they are being requested toexert during stimulation will greatly improve device usability anddecrease the risk of using the device on the patient. If the patient isrepositioned during therapy stimulation may longer be effective.Alerting the user to this affect will ensure continuation of therapy andmake the device more usable. The ICU is a complicated environment anddeskilling the detecting of fault conditions is critical to usability.Detecting such fault conditions are only possible if the correctmeasurements and detections methods are made. It is also important tonot make the detection too sensitive such that false positive alarms aredetected.

Definitions

In the field of respiration there is not complete uniformity in the useof terms or nomenclature. This especially true with ventilation modeswhere manufacturers describe operation in terms of company specificnomenclature. To clarify the disclosure the following terms should begiven the ascribed meaning in interpreting this document.

Work of Breathing—in this disclosure relates to the energy expended toinhale a breathing gas. It is usually expressed as work per unit volume,for example, joules/liter, or as a work rate (power), such asjoules/min. In most instances the term relates to a single breath. Inmost literature it is measured over several breaths.

Work—It is usually expressed as work joules or it may also be expressedas the work per unit volume, for example, joules/liter.

Power—defines as the rate of work such as joules/min

Equation of Motion for Respiration is used to describe the pressuresexerted by the compliance and resistive forces of the lung.

Selected breath. The stimulator controller intervenes by selecting abreath to stimulate this is done by selecting every other breath insimple ratio of 1:2 up to about a one of every twenty breaths (1:20)

Predecessor breath is the breath immediately prior to a selected breath.

Subsequent breath is the breath immediately after a selected breath.

Companion breath. From the perspective of a selected breath bothpredecessor breaths and subsequent breaths are defined as companionbreaths. In essence all non selected breaths are companion breaths withthe immediately following and preceding breaths given unique names.

Pressure control modality—is a mode of mechanical ventilation alone anda variable within other modes of mechanical ventilation. Pressurecontrol is used to regulate pressures applied during mechanicalventilation. During Pressure Control Ventilation, the control parameteris pressure and flow is adjusted to reach the specified pressure.

Flow control modality—is used in Volume Control Ventilation. Variousflow control modes may be used such as square wave or descending ramp.During Volume Control Ventilation, the control parameter is flow andpressure is a resultant parameter.

SIMV—Synchronized intermittent mechanical ventilation (SIMV) is avariation of IMV, in which the ventilator breaths are synchronized withpatient inspiratory effort if the patient is making an effort toinspire. The breath mode is most often a mandatory breath mode pairedwith a spontaneous breath mode.

SIMV (Volume Control, PSV)—In this SIMV case the mandatory or assistmode of ventilation is a Volume Control breath with a spontaneous modeof Pressure Support Ventilation.

SIMV (Pressure Control, PSV)—In this SIMV case the mandatory or assistmode of ventilation is a Pressure Control breath with a spontaneous modeof Pressure Support Ventilation.

Bi-level Ventilation—Bilevel positive airway pressure (BPAP), commonlyreferred to by the trademarked names BiPAP and BiPAP, is a form ofnon-invasive mechanical pressure support ventilation that uses atime-cycled or flow-cycled change between two different applied levelsof positive airway pressure.

PEEP—Positive end-expiratory pressure (PEEP) is the pressure in thelungs (alveolar pressure) above atmospheric pressure (the pressureoutside of the body) that exists at the end of expiration.

Mandatory Breath—A breath for which either the timing or size iscontrolled by a ventilator; the machine initiates (i.e., triggers) orterminates (i.e., cycles) the breath.

Spontaneous Breath—During mechanical ventilation, a breath for whichboth the timing and the size are controlled by the patient (i.e., thebreath is both initiated [triggered] and terminated [cycled] by thepatient).

PRVC (Pressure Regulated Volume Control)—is a controlled mode ofventilation which combines pressure and volume controlled ventilation. Apreset tidal volume is delivered at a set rate, similar to VC, but it isdelivered with the lowest possible pressure.

The above disclosure is intended to be illustrative and not exhaustive.This description will suggest many variations and alternatives to one ofordinary skill in this field of art. All these alternatives andvariations are intended to be included within the scope of the claimswhere the term “comprising” means “including, but not limited to.” Thosefamiliar with the art may recognize other equivalents to the specificembodiments described herein which equivalents are also intended to beencompassed by the following numbered paragraphs, as well as in theclaims below.

Paragraph 1. A lead system for use with a PEPNS system comprises thefollowing elements: A first lead having a housing, the housingcontaining at least two or more pacing electrodes spaced apart in alinear arrangement; and an identifying resistor. Each of the pacingelectrodes and identifying resistor being in separate electricalcommunication with a controller of the PEPNS system.

Paragraph 2. The system of paragraph 1 further comprising a second lead.

Paragraph 3. The system of paragraph 2 wherein the controller comprisesan electrical pulse generator. Each electrode is in electricalcommunication with electrical pulse generator.

Paragraph 4. The system of paragraph 3 wherein the controller comprisesa CPU and a GUI. The CPU is in electrical communication with eachelectrode, each identifying resistor, and the pulse generator. The CPUcontrols the characteristics of an electrical pulse sent to the firstlead and the second lead. The GUI in electronic communication with theCPU.

Paragraph 5. A medical device for use with a mechanical ventilator whereboth the device and the ventilator are coupled to a patient; the medicaldevice comprises: A multiple pole electrode set located on a lead. Thelead is positioned subcutaneously and proximate at least one phrenicnerve in the neck of the patient. A stimulator/controller connected tothe lead for selecting one electrode pair from the multiple poleelectrode set, and defining a selected electrode pair and for deliveringelectrical stimulation to the selected electrode pair of the electrodeset, according to a set of input electrical parameters that set a pulserepetition rate, a current amplitude, a pulse width, a pulse waveform, astimulation pulse train waveform. The input electrical parameterssufficient to at least partially activate the patient's diaphragm. Aninstrumented wye coupled to the patient and coupled to the mechanicalventilator providing a wye flow measurement and a wye pressuremeasurement to the stimulator/controller. The stimulator/controllerselecting one of several breaths, to define a single selected breath.The stimulator/controller initiating electrical stimulation in thesingle selected breath at the time that corresponds to a beginning ofinspiration event triggered by a wye flow measurement. Thestimulator/controller terminating electrical stimulation in the singleselected breath at the time corresponding to an end of inspiration eventtriggered by the wye flow measurement. The beginning of the inspirationevent of the selected breath and the end of inspiration event of theselected breath together setting a duration for the electricalstimulation within the inspiratory phase of a single selected breathcycle. A power/work measuring device within the stimulator/controllerand coupled to the instrumented wye receiving a measured wye flow value,and a wye pressure value, defining a set of instrumented wyemeasurements. The power/work measurement device using the wyemeasurements along with a measure of lung compliance and a measure oflung resistance of the patient to predict a pressure curve in the wyeover the duration. The power/work measurement device comparing theactual wye pressure curve to the predicted wye pressure curve andforming the difference between the predicted wye pressure and the actualmeasured wye pressure defining a Pmus value. The power/work measurementdevice using the Pmus value along with a measure of lung compliance anda measure of lung resistance of the patient to compute a work ofbreathing curve for the selected inspiratory phase of the singleselected breath defining a work/power curve. The work/power curverepresenting the instantaneous work and associated time based powermeasurement representing the total power expended by the patient duringthe inspiratory duration of the selected breath without regard to thecontribution to work performed by the mechanical ventilator.

Paragraph 6. A medical device for use with a mechanical ventilator,wherein both the device and the ventilator are coupled to a patient; themedical device comprises: A subcutaneous electrode pair positionedproximate at least one phrenic nerve in the neck of the patient. Astimulator/controller delivering electrical stimulation to the electrodepair at a pulse repetition rate, with a current and a waveformsufficient to at least partially activate the patient's diaphragm. Aninstrumented wye coupled to the patient and coupled to the mechanicalventilator, providing a wye flow measurement and a wye pressuremeasurement to the stimulator/controller. The stimulator/controllerselecting one of several breaths defining a selected breath. Thestimulator/controller beginning stimulation at the beginning of aninspiratory event in response to an inspiratory trigger event, the eventcorresponding to a preset specific flow at the instrumented wye. Thestimulator/controller ending stimulation at the end of an concludedinspiratory event triggered by an end inspiratory trigger event, theevent corresponding to a specific flow at the instrumented wye. Theinspiratory event trigger and the end inspiratory event trigger andtogether defining a duration for the stimulation within the inspiratoryphase of a single selected breath. A power/work measuring device coupledto the instrumented wye measuring the instantaneous work throughout theinspiratory phase of the single breath, by comparing a predictedpressure at the wye and a measured pressure at the wye, and indicatingwork only if the predicted pressure differs from the measured pressureat the instrumented wye.

Paragraph 7. The device of paragraph 6 wherein the inspiratory triggeris a patient initiated event.

Paragraph 8. The device of paragraph 6 wherein the end inspiratorytrigger is a patient initiated event.

Paragraph 9. The device of paragraph 6 wherein the inspiratory triggeris a mechanical ventilator initiated event.

Paragraph 10. The device of paragraph 6 wherein the end inspiratorytrigger is a mechanical ventilator initiated event.

Paragraph 11. The device of paragraph 6 further including an indicatorpresenting the level of stimulation delivered during the inspirationphase of the breath.

Paragraph 12. The device of paragraph 6 further including an indicatorpresenting the measured total power and total work for the level ofstimulation delivered during the inspiration phase of the breath.

Paragraph 13. A medical device system for use with a mechanicalventilator, wherein both the system and the ventilator are coupled to apatient; the medical device system comprises: A mechanical ventilatoroperable in pressure control modes. A temporary electrode pairpositioned subcutaneous and proximate at least one phrenic nerve in theneck of the patient. A stimulator/controller connected to electrode pairof the electrode set, according to a set of input electrical parametersthat set a repetition rate, a current amplitude, a pulse width, a pulsewaveform, a stimulation pulse train waveform, the input electricalparameters sufficient to at least partially activate the patient'sdiaphragm. The stimulator/controller including a power/work measurementdevice. An instrumented wye coupled to the patient and providing a wyeflow measurement and a wye pressure measurement to the power/workmeasurement device within the stimulator/controller. Thestimulator/controller selecting one of several breaths, defining aselected breath. The selected breath followed by a subsequent breath,defining a subsequent breath. The stimulator/controller initiatingelectrical stimulation at the beginning of the selected breath thatcorresponds to an inspiratory event triggered by a wye flow measurement.The stimulator/controller terminating electrical stimulation at the endof an inspiratory event triggered by the wye flow measurement. Thebeginning inspiratory event of the selected breath and the endinginspiratory event of the selected breath together setting a stimulationduration for the inspiratory phase of the single selected breath. Apower/work measuring device within the stimulator/controller and coupledto the instrumented wye receiving wye pressure and flow measurement anddisplaying a positive value for work during a stimulated breath. Themechanical ventilator initiating a pressure control subsequent breath.The mechanical ventilator terminating the subsequent pressure controlbreath defining a pressure control subsequent breath duration having acharacteristic pressure control profile. The power/work measurementdevice determining a zero value for work during the subsequent pressurecontrol breath.

Paragraph 14. A medical device system for use with a mechanicalventilator both coupled to a patient, the medical device systemcomprises: A mechanical ventilator operable in volume control modes. Atemporary electrode pair positioned subcutaneously and proximate to atleast one phrenic nerve in the neck of the patient. Astimulator/controller connected to electrode pair of the electrode set,according to a set of input electrical parameters that set a repetitionrate, a current amplitude, a pulse width, a pulse waveform, astimulation pulse train waveform. The input electrical parameterssufficient to at least partially activate the patient's diaphragm. Thestimulator/controller including a power/work measurement device. Aninstrumented wye coupled to the patient providing a wye flow measurementand a wye pressure measurement to the power/work measurement devicewithin the stimulator/controller. The stimulator/controller selectingone of several breaths, defining a selected breath. The selected breathfollowed by subsequent next breath, defining a sequential breath. Thestimulator/controller initiating electrical stimulation at the beginningof the selected breath that corresponds to an inspiratory eventtriggered by a wye flow measurement. The stimulator/controllerterminating electrical stimulation at the end of an inspiratory eventtriggered by the wye flow measurement. The beginning inspiratory eventof the selected breath and the ending inspiratory event of the selectedbreath together setting a duration for the electrical stimulation withinthe inspiratory phase of a single selected breath cycle. A power/workmeasuring device within the stimulator/controller and coupled to theinstrumented wye receiving wye pressure measurement and displaying apositive value for work during a stimulated breath. The mechanicalventilator initiating a volume control breath. The power/workmeasurement device using the wye pressure measurement and displaying azero value for work during the volume control breath.

Paragraph 15. A method of stimulating a diaphragm to provoke motion ofthe diaphragm during inspiration comprises the following steps:

-   -   a. stimulating the phrenic nerve at a set level during a        selected breath of a patient;    -   b. obtaining a measurement of the diaphragm work exerted by the        patient for the inspiratory breath cycle of a selected breath of        a patient;    -   c. modifying the stimulation signal if the actual value of        diaphragm work is outside the selected range of the desired        value of diaphragm work; and repeating steps a-c.

Paragraph 16. A medical device for use with a mechanical ventilatorwherein both are coupled to a patient. The medical device comprises: Amultiple pole electrode set located on a lead, wherein the lead ispositioned subcutaneously and proximate to at least one phrenic nerve inthe neck of the patient. A stimulator/controller connected to the leadfor selecting one electrode pair from the multiple pole electrode setdefining a selected electrode pair and for delivering electricalstimulation to the selected electrode pair of the electrode set,according to a set of input electrical parameters that set a pulserepetition rate, a current amplitude, a pulse width, a pulse waveform, astimulation pulse train waveform. The input electrical parameterssufficient to at least partially activate the patient's diaphragm. Aninstrumented wye coupled to the patient and coupled to the mechanicalventilator providing a wye flow measurement and a wye pressuremeasurement to the stimulator/controller. The stimulator/controllerselecting one of several breaths, defining a single selected breath. Thestimulator/controller initiating electrical stimulation at the beginningof the selected breath that corresponds to an inspiratory eventtriggered by a wye flow measurement. The stimulator/controllerterminating electrical stimulation at the end of an inspiratory eventtriggered by the wye flow measurement. The beginning inspiratory eventof the selected breath and the ending inspiratory event of the selectedbreath together setting a duration for the electrical stimulation withinthe inspiratory phase of a single selected breath cycle. A power/workmeasuring device within the stimulator/controller and coupled to theinstrumented wye receiving a measured wye flow value, and a wye pressurevalue, defining a set of instrumented wye measurements. The power/workmeasurement device using the wye measurements along with a measure oflung compliance and a measure of lung resistance of the patient topredict a pressure curve for the selected inspiratory phase of theselected breath defining a predicted wye pressure curve. The power/workmeasurement device comparing the actual wye pressure value to thepredicted wye pressure curve and forming the difference between thepredicted wye pressure and the actual measured wye pressure defining aPmus value. The power/work measurement device using the Pmus value alongwith a measure of lung compliance and a measure of lung resistance ofthe patient to compute a work of breathing curve for the selectedinspiratory phase of the single selected breath defining a work/powercurve. The work/power curve representing the instantaneous work andassociated time based power measurement representing the total powerexpended by the patient during the inspiratory phase of the selectedbreath without regard to the contribution to work performed by themechanical ventilator.

Paragraph 17. A medical device for use with a mechanical ventilator bothcoupled to a patient. The medical device comprises: A subcutaneouselectrode pair positioned proximate at least one phrenic nerve in theneck of the patient. A stimulator/controller delivering electricalstimulation to the selected electrode pair at a pulse repetition rate,with a current and a waveform sufficient to at least partially activatethe patient's diaphragm. An instrumented wye coupled to the patientproviding a wye flow measurement and a wye pressure measurement to thestimulator/controller. The stimulator/controller selecting one ofseveral breaths defining a selected breath. The stimulator/controllerbeginning stimulation at the beginning of a patient initiatedinspiratory event triggered by flow at the wye. Thestimulator/controller ending stimulation at the end of a patientconcluded inspiratory event triggered by flow at the wye. The patientinitiated inspiratory event and the patient concluded inspiratory eventthereby setting a duration for the stimulation within the inspiratoryphase of a single selected patient initiated breath cycle. A power/workmeasuring device coupled to the instrumented wye measuring theinstantaneous work throughout the inspiratory phase of the singlebreath, by comparing a predicted pressure at the wye and a measuredpressure at the wye, and indicating work only if the predicted pressurediffers from the measured pressure in the wye. An indicator presentingthe level of stimulation delivered during the inspiration phase of thebreath. An indicator presenting the measured total power and total workfor the level of stimulation delivered during the inspiration phase ofthe breath.

Paragraph 18. A medical device for use with a mechanical ventilator bothcoupled to a patient. The medical device comprises: A subcutaneouselectrode pair positioned proximate at least one phrenic nerve in theneck of the patient. A stimulator/controller delivering electricalstimulation to the selected electrode pair at a pulse repetition rate, acurrent and a waveform sufficient to at least partially activate thepatient's diaphragm. An instrumented wye coupled to the patientproviding a wye flow measurement and a wye pressure measurement to thestimulator/controller. The stimulator/controller selectingstimulator/controller g one of several breaths defining a selectedbreath. The stimulator/controller beginning stimulation at the beginningof the a patient initiated inspiratory event triggered by flow at thewye. The stimulator/controller ending stimulation at the end of amechanical ventilator concluded inspiratory event triggered by flow atthe wye. The patient initiated inspiratory event and the mechanicalventilator concluded inspiratory event thereby setting a duration forthe stimulation within the inspiratory phase of a single selectedpatient initiated breath cycle. A power/work measuring device coupled tothe instrumented wye measuring the instantaneous work throughout theinspiratory phase of the single breath, by comparing a predictedpressure at the wye and a measured pressure at the wye, and indicatingwork only if the predicted pressure differs from the measured pressurein the wye. An indicator presenting the level of stimulation deliveredduring the inspiration phase of the breath. An indicator presenting themeasured total power and total work for the level of stimulationdelivered during the inspiration phase of the breath.

Paragraph 19. A medical device for use with a mechanical ventilator bothcoupled to a patient. The medical device comprises: A subcutaneouselectrode pair positioned proximate at least one phrenic nerve in theneck of the patient. A stimulator/controller delivering electricalstimulation to the selected electrode pair at a repetition rate, with avoltage, a current and a waveform sufficient to at least partiallyactivate the patient's diaphragm. An instrumented wye coupled to thepatient providing a wye flow measurement and a wye pressure measurementto the stimulator/controller. The stimulator/controller selecting one ofseveral breaths defining a selected breath. The S/C beginningstimulation at the beginning of the mechanical ventilator initiatedinspiratory event triggered by flow at the wye. Thestimulator/controller ending stimulation at the end of a mechanicalventilator concluded inspiratory event triggered by flow at the wye. Thepatient initiated inspiratory event and the patient concludedinspiratory event thereby setting a duration for the stimulation withinthe inspiratory phase of a single selected patient initiated breathcycle. A power/work measuring device coupled to the instrumented wyemeasuring the instantaneous work throughout the inspiratory phase of thesingle breath, by comparing a predicted pressure at the wye and ameasured pressure at the wye, and indicating work only if the measuredpressure exceeds the predicted pressure in the wye. An indicatorpresenting the level of stimulation delivered during the inspirationphase of the breath. An indicator presenting the measured total powerand total work for the level of stimulation delivered during theinspiration phase of the breath.

Paragraph 20. A medical device for use with a mechanical ventilator bothcoupled to a patient. The medical device comprises: A subcutaneouselectrode pair positioned proximate at least one phrenic nerve in theneck of the patient. A stimulator/controller delivering electricalstimulation to the selected electrode pair at a pulse repetition rate, acurrent and a waveform sufficient to at least partially activate thepatient's diaphragm. An instrumented wye coupled to the patientproviding a wye flow measurement and a wye pressure measurement to thestimulator/controller. The stimulator/controller selecting one ofseveral breaths defining a selected breath. The stimulator/controllerbeginning stimulation at the beginning of the mechanical ventilatorinitiated inspiratory event triggered by flow at the wye. Thestimulator/controller ending stimulation at the end of a patientconcluded inspiratory event triggered by flow at the wye. The ventilatorinitiated inspiratory event and the patient concluded inspiratory eventthereby setting a duration for the stimulation within the inspiratoryphase of a single selected patient initiated breath cycle. A power/workmeasuring device coupled to the instrumented wye measuring theinstantaneous work throughout the inspiratory phase of the singlebreath, by comparing a predicted pressure at the wye and a measuredpressure at the wye, and indicating work only if the predicted pressurediffers from the measured pressure in the wye. An indicator presentingthe level of stimulation delivered during the inspiration phase of thebreath. An indicator presenting the measured total power and total workfor the level of stimulation delivered during the inspiration phase ofthe breath.

Paragraph 21. The medical device of paragraph 9 which further comprises:A display presenting the level of stimulation delivered during theinspiration phase of the breath. A display presenting the measured totalpower and total work for the level of stimulation delivered during theinspiration phase of the breath.

Paragraph 22. A medical device system for use with a mechanicalventilator both coupled to a patient. The medical device systemcomprises: A mechanical ventilator operable in both pressure control andvolume control modes. A temporary electrode pair positioned subcutaneousand proximate at least one phrenic nerve in the neck of the patient. Astimulator/controller connected to electrode pair of the electrode set,according to a set of input electrical parameters that set a repetitionrate, a current amplitude, a pulse width, a pulse waveform, astimulation pulse train waveform, the input electrical parameterssufficient to at least partially activate the patient's diaphragm; thestimulator/controller including a power/work measurement device. Aninstrumented wye coupled to the patient providing a wye flow measurementand a wye pressure measurement to the power/work measurement devicewithin the stimulator/controller. The stimulator/controller selectingone of several breaths, defining a selected breath. The selected breathfollowed by subsequent next breath, defining a sequential breath. Thestimulator/controller initiating electrical stimulation at the beginningof the selected breath that corresponds to an inspiratory eventtriggered by a wye flow measurement. The stimulator/controllerterminating electrical stimulation at the end of an inspiratory eventtriggered by the wye flow measurement. The beginning inspiratory eventof the selected breath and the ending inspiratory event of the selectedbreath together setting a duration for the electrical stimulation withinthe inspiratory phase of a single selected breath cycle. A power/workmeasuring device within the stimulator/controller and coupled to theinstrumented wye receiving wye pressure and flow measurement anddisplaying a positive value for work during a stimulated breath. Themechanical ventilator initiating a pressure control breath. Themechanical ventilator terminating a pressure control breath at the wye.The beginning and ending forming a duration having a characteristicpressure profile. The power/work measurement device using the wyepressure measurement and displaying a zero value for work during anun-stimulated pressure control breath.

Paragraph 23. A medical device system for use with a mechanicalventilator both coupled to a patient. The medical device systemcomprises: A mechanical ventilator operable in both pressure control andvolume control modes. A temporary electrode pair positionedsubcutaneously and proximate to at least one phrenic nerve in the neckof the patient. A stimulator/controller connected to electrode pair ofthe electrode set, according to a set of input electrical parametersthat set a repetition rate, a current amplitude, a pulse width, a pulsewaveform, a stimulation pulse train waveform, the input electricalparameters sufficient to at least partially activate the patient'sdiaphragm; the stimulator/controller including a power/work measurementdevice. An instrumented wye coupled to the patient providing a wye flowmeasurement and a wye pressure measurement to the power/work measurementdevice within the stimulator/controller. The stimulator/controllerselecting one of several breaths, defining a selected breath. Theselected breath followed by subsequent next breath, defining asequential breath. The stimulator/controller initiating electricalstimulation at the beginning of the selected breath that corresponds toan inspiratory event triggered by a wye flow measurement. Thestimulator/controller terminating electrical stimulation at the end ofan inspiratory event triggered by the wye flow measurement. Thebeginning inspiratory event of the selected breath and the endinginspiratory event of the selected breath together setting a duration forthe electrical stimulation within the inspiratory phase of a singleselected breath cycle. A power/work measuring device within thestimulator/controller and coupled to the instrumented wye receiving wyepressure measurement and displaying a positive value for work during astimulated breath. The mechanical ventilator initiating a volume controlbreath. The power/work measurement device using the wye pressuremeasurement and displaying a zero value for work during an un-stimulatedvolume control breath.

Paragraph 24. A method of stimulating a diaphragm to provoke motion ofthe diaphragm during inspiration comprises the following steps:

-   -   a. obtaining a measurement of the work exerted for the        inspiratory breath cycle of a selected breath of a patient;    -   b. setting a desired value for the level of work during        contraction of the diaphragm, transmitting a stimulation signal        to an electrode positioned within subcutaneous tissue of the        patient such that the electrode recruits a phrenic nerve of the        patient and contracts the diaphragm;    -   c. after transmitting the stimulation signal, determining the        actual work generated by the diaphragm;    -   d. as a function of wye flow, pressure and patient resistance        and compliance and maintaining the stimulation signal valve for        later selected breaths if the actual value of the level of the        diaphragm work is within a selected range of the desired value;

or modifying the stimulation signal if the actual value of diaphragmwork is outside the selected range of the desired value of diaphragmwork; and repeating steps a-d.

What is claimed is:
 1. A medical device for use with a mechanicalventilator and breathing circuit coupled to a patient, said medicaldevice comprising: a subcutaneous electrode pair positioned proximate atleast one phrenic nerve in the neck of said patient; astimulator/controller connected to said electrode pair via a lead cable,said stimulator/controller delivering electrical stimulation to saidelectrode pair at a pulse repetition rate, with a current and a waveformsufficient to at least partially activate the patient's diaphragm; aninstrumented wye coupled to said patient and coupled to said mechanicalventilator via tubing of the breathing circuit, providing a wye flowmeasurement and a wye pressure measurement to saidstimulator/controller; said stimulator/controller selecting one ofseveral breaths defining a single selected breath; saidstimulator/controller beginning stimulation at the beginning of aninspiratory event in response to an inspiratory trigger event, saidevent corresponding to a preset specific flow at said instrumented wye;said stimulator/controller ending stimulation at the end of aninspiratory event triggered by an end inspiratory trigger event, saidevent corresponding to a specific flow at said instrumented wye; saidinspiratory event trigger and said end inspiratory event triggertogether defining a duration for the stimulation within the inspiratoryphase of said single selected breath; a power/work measuring devicecoupled to said instrumented wye measuring the instantaneous workthroughout the inspiratory phase of said single selected breath, bycomparing a predicted pressure at the wye and a measured pressure at thewye, and indicating work only if the predicted pressure differs from themeasured pressure at said instrumented wye.
 2. The device of claim 1wherein said inspiratory trigger event is a patient initiated event. 3.The device of claim 1 wherein said end inspiratory trigger event is apatient initiated event.
 4. The device of claim 1 wherein saidinspiratory trigger event is a mechanical ventilator initiated event. 5.The device of claim 1 wherein said end inspiratory trigger event is amechanical ventilator initiated event.
 6. The device of claim 1 furtherincluding: an indicator presenting the level of stimulation deliveredduring said duration of the single selected breath.
 7. The device ofclaim 1 further including: an indicator presenting the measured totalpower and total work for the level of stimulation delivered during thesaid duration of said single selected breath.